Whether any of the biological effects associated with coca chewing as practiced by the Andean natives helps to maintain or disrupt body homeostasis particularly with regard to overall body metabolism is an unsettled issue of the "coca problem". These effects could be due to the cocaine released from the coca, or its metabolites, or to some substance formed from the cocaine during the chewing process. Complicating the "coca problem" is the lack of basic information on how the body handles cocaine ingested orally compared with cocaine injected. It is planned (1) to elaborate the pharmacokinetics of cocaine and its several metabolites: ecgonine methyl ester, benzoyl ecgonine and ecgonine in the dog given intravenously and orally, and (2) to study their effects on the relative utilization of fats and carbohydrates in the rat at different levels of nutrition. The current research effort has concentrated on continuing the development of a suitable assay for cocaine and related ecgonine alkaloids in urine. Having a reliable, sensitive assay is crucial to the proposed pharmacokinetic studies. We have been able to obtain linear standard curves for a concentration range of 20 ng to 160 ng for each compound injected into the gas chromatograph. Recovery studies from spiked aqueous samples show reasonable linearity. Experiments are underway to assess the efficiency of extraction of the four compounds from spiked urine samples. Experiments are also underway to confirm the significant depression in the respiratory quotient (RQ) found in rats fed a low protein-high carbohydrate diet containing cocaine, ecgonine methyl ester or benzoyl ecgonine. The latter finding suggests that the coca-derived ecgonine alkaloids may have a direct regulating role in body metabolism.